| First Author | Kitajima Y | Year | 2020 |
| Journal | Front Cell Dev Biol | Volume | 8 |
| Pages | 859 | PubMed ID | 32984340 |
| Mgi Jnum | J:301728 | Mgi Id | MGI:6506286 |
| Doi | 10.3389/fcell.2020.00859 | Citation | Kitajima Y, et al. (2020) Inducible Rpt3, a Proteasome Component, Knockout in Adult Skeletal Muscle Results in Muscle Atrophy. Front Cell Dev Biol 8:859 |
| abstractText | The ubiquitin-proteasome system has the capacity to degrade polyubiquitinated proteins and plays an important role in many cellular processes. However, the role of Rpt3, a crucial proteasomal gene, has not been investigated in adult muscles in vivo. Herein, we generated skeletal-muscle-specific Rpt3 knockout mice, in which genetic inactivation of Rpt3 could be induced by doxycycline administration. The Rpt3-knockout mice showed a significant reduction by more than 90% in the expression of Rpt3 in adult muscles. Using this model, we found that proteasome dysfunction in adult muscles resulted in muscle wasting and a decrease in the myofiber size. Immunoblotting analysis showed that the amounts of ubiquitinated proteins were markedly higher in muscles of Rpt3-deficient mice than in those of the control mice. Analysis of the autophagy pathway in the Rpt3-deficient mice showed that the upregulation of LC3II, p62, Atg5, Atg7, and Beclin-1 in protein levels, which supposed to be compensatory proteolysis activation. Our results suggest that the proteasome inhibition in adult muscle severely deteriorates myofiber integrity and results in muscle atrophy. |
